Do You Enjoy The Darker Side of Things?

This is an inquiry piece because I’m interested in light surveys of how people with mental illness differ from people I consider “normal”. Yesterday I was interested in the different mood states that may fall outside the usual mania-depression model. Today, I’m interested in whether our minds are a little darker than others.

The inspiration for this comes from my girlfriend and our new roommate, along with the movie Hunger Games (which I desperately want to rant about, but I’ll refrain). If you don’t care to hear how this started and the anecdotal evidence that I have, you can skip to the end.

To give some background, my girlfriend has suffered from severe depression in her life at least once, if not a few times. And she and I share a very dark perspective on things. I didn’t like Schindler’s List because I thought it was too fluffy (and art-house gimmicky). We both love metal and incredibly angry music in that we find these things relaxing. And after watching a movie like The Last Circus, I was giddy with happiness and she was grinning from ear to ear. This is a movie about two murderous clowns in fascist Spain who lose their minds and enter into a bloody back and forth to woo their masochistic woman of interest. We thought the movie was great. We both enjoy the darker things in life and even have an aversion to things that are too sweet. That’s me and her.

Now our new roommate and I went to see the Hunger Games. I wasn’t expecting to like it, and the cinematography did indeed suck, but I was willing to give it a try. If you’re not familiar with it, the main idea is this: in order to punish an old uprising, the provinces are required every year to submit two children, male and female, between the ages of 12 and 18, to compete to the death against all the other “tributes”. Only one will survive and will be declared the winner. Sounds deliciously dark in a Battle Royale kind of way (by the way, that’s a great Japanese comedy about children killing each other). But, and this is a spoiler alert so don’t read any further if you really want to see it (but it’s not a big spoiler), the main character never kills anyone with intent.

My new roommate and I got into a disagreement over this in that she liked that the main character didn’t have to really kill anyone. The way that I saw it, it was a cop out. In a life or death situation where people are hunting you to kill you and will not cease until they find you or you kill them, chances are you’re going to commit some degree of premeditated killing. And the movie would have been the better for it. It would have been darker and gotten into the psychology of what these games do to people. It would have made the spectacle of it, even the idea of us watching it, something closer to perverse. But that’s not what my roommate wanted, she wanted something lighter.

And this I’ve noticed in other members of my family. None of them have that much of a dark side. And while some do like darker things, like preferring the Empire Strikes Back over New Hope, there isn’t that cold relishing of the darker things that my girlfriend and I appear to have.

So the question is quite clear, hopefully, at this point. And it applies to anyone with a mental illness because I’m interested in it across the board. The question(s) are: do you enjoy darker things more than other people you know,

if you had to choose between a movie that was dark and one that was fluffier which would you pick,

do movies/books/music that make these leaps into darker material not only please you but excite you,

and finally, have you noticed a divide between tastes in people who are mentally ill and those without a mental illness?

Treatment of Treatment Resistant Bipolar

I was browsing over a Psychiatric Times article about treatment resistance in bipolar disorder and how to define it. The article requires that you register, and it’s a hefty read, so I’ll give you the run down of what it says.

First of all, treatment resistant bipolar disorder is common under their definition, which is symptom recurrence in 2 years under maintenance. That’s definition number one. But definition number two concerns how to regard resistance to acute episodes, rather than just the long term.

For acute resistance, it is proposed by GS Sachs that resistance should be characterized  as a patient who does not respond to two standard medications over a period of time, for example, 6 weeks for mania.

But the article is not particularly fond of a straight forward approach like Sachs. The reason is that most people with bipolar disorder require more than 1 medication, which implies resistance in the general BP population. Secondly, there is no single mechanism that the drugs work by. Additionally, they cite that evidence for combining is lacking and the dosing in such combinations is lacking. So in the end, there is little in the way of evidence base approaches to defining treatment resistance.

But they do go ahead and acknowledge treatment resistance as occurring. It appears from the article that they subscribe to the 2 years of remission definition. And treatment should be based around evidence based treatments for the particular episode. They have a nifty table for this as well. 

They suggest that should monotherapy fail, one can start combining these treatments. I got my combo, lithium, abilify, and zyprexa (though abilify didn’t work).

Depression is another beast. They recommend antidepressants with antimanic drugs. They also point to evidence some very interesting evidence by GS Leverich that SNRIs, like welbutrin, might cause a depression-mania switch to be even more likely than SSRIs, like prozac. Never would have thought that.

What about maintenance then? Psychiatric Times says that the most common approach is to just leave the medications at their acute levels and reduce as needed according to tolerance. Personally, I’m at the opposite end of this approach. My psychiatrist wants to get me off of everything but lithium and add back in as needed. I agree with her approach in my case because I have been medicated to me ears and I’d like to start over and find what works. This is also a good approach because A Cipriani, lithium is the only medication so far to have possible antisuicidal effects. So lithium’s good in my book. But there are some reasons to not follow suit with what my psychiatrist is doing. If lithium works it might be only because of the zyprexa in there. There is some research showing that combination therapy might work where each individual medication failed. But there’s only one way to know, and that’s to give it a try.

It’s really an interesting article, and you should go read it if you have the time. I just thought I’d distill the main qualities of the paper so you don’t have to read the entire thing. What I found interesting was how by the book I was treated, and how by the book can add up to a lot of pills very quickly. It is also interesting to see the difference in approach that my psychiatrist has in treating me versus what apparently most doctors do, which is leave the levels at the point that they take care of the acute symptoms. I wouldn’t be able to function properly and would have very expensive bills to pay if I did that. So, in tandem with what I wrote earlier, it seems that I’m on a minimalist diet of pills, only time will tell if that works.

Lithium – Side Effects and Myths

It was blod tests today for me, and now after taking my morning dose of lithium, I’m back to a lethargic couch potato. So I thought I’d write a bit about lithium’s side effects and give a face to what they are actually like, rather than scribbled down on a sheet of paper.

On the mild/minor side effect list are tremor , blurred vision, dry mouth, fatigue, cardiac arrhythmias, polyuria and muscle weakness are additional common lithium side effects. In terms of hunger and the like, lithium side effects include anorexia, diarrhea, vomiting, and nausea.

I have the tremor, dry mouth, fatigue, muscle weakness, diarrhea (sorry, TMI), and am slowly developing anorexia.

What is meant by a tremor is simply that with no load on your muscles, your hands shake. With a great deal of relaxation and concentration, the tremor can subside. But if there is a load on the muscles, then they begin shaking rapidly. It’s a lot like having too much coffee. Your hands are just not as responsive or accurate as they shake all the time.

Dry mouth, doesn’t sound horrible, but it’s actually fairly grating on the nerves. It’s like having cotton balls in your cheeks all the time. No matter how much you drink, it still feels like a desert in your mouth.

But, by far the worst that I’ve noticed are fatigue and muscle weakness. Walking 60 minutes today (which is not that bad usually) I found my legs trembling as I got home. Stairs are also difficult. I have to stabilize myself in order to get down them properly, otherwise my legs will shake too much. The fatigue is also a killer. About 1.5 hours after taking my pills and I need to close my eyes. And no amount of coffee helps with this. It’s also a different fatigue than other pills. When abilify first started off, it knocked me out cold. It was just bare sleeping and unable to move. But lithium is not like the antipsychotic type of fatigue, it’s closer to klonopin. I start feeling really warm and calm and just want to get comfortable so I can doze off for a few minutes. But it’s also different from klonopin in that I don’t feel drugged, I just feel sleepy.

Lithium is also making me more hazy. I just feel slowed down. But I might also be ADD and this is impacting it in some way.  It’s also a definite side effect of fatigue. If you’re tired then no matter what you’ll feel cognitively slower and not want to do cognitively heavy loads.

One thing that lithium does not do is cause memory loss, it is a myth. A quick pubmed search revealed an older study, but a good one. It is a 6 year longitudinal study that followed 18 people, all on lithium for quite some time. The result was that only 1 out of 10 tests showed any decrease. It was a statistically significant drop, but one corrected for by age. After all, over time BP grinds one’s mind down. Additionally, subjects who complained of cognitive impairment, often exhibited mild depression. So in short, lithium doesn’t cause memory loss like it usually is thought to. It is a myth.

 

http://www.ncbi.nlm.nih.gov/pubmed/3379146

Theory of Mind and Bipolar Disorder

In a study done by N. Karr, theory of mind deficits were studied in people with bipolar disorder. Theory of mind is a concept invented by philosophers. Having a theory of mind is having an ability to attribute things like desires, beliefs, and other mental states to people beyond one’s own mind. So the study focuses on how well individuals with bipolar disorder can attribute correct desires and beliefs to other people.

The test is a simple one designed originally for schizophrenics by Christopher Frith. The test consists of 6 stories that are read and simultaneously shown a series of cartoons depicting what was happening. All the stories involved some degree of deception and two questions were asked, one “reality” which was about the story, and one theory of mind question about the mental states of someone in the story. In the study with bipolar patients, there were first order and second order questions. First order questions are questions like “what did X believe happen”, while a second order question would be “what belief did X have about what he believed?” Second order theory of mind questions revolve around what mental states we have with respect to other mental states rather than about something in reality.

Still with me? Good, I’ll try to clarify with comments on this one since first-order/second-order stuff can get very confusing very quickly. The best way to think is that second order states are things like how strongly one believes something to be true. That is, you believe that X is the case, but you believe that you believe weakly that X is the case. And if you don’t get it, don’t feel bad, it’s something that a lot of peple struggle with, myself included.

The last set up for this experiment was a comparison of theory of mind capabilities throughout mania, depression, and remission. The results were interesting:

As you can see, normal people were able to interpret the mental states of others without difficulty. However, across the board there were deficiencies in individuals with bipolar disorder. Particularly interesting to me is that depressed individuals score higher than manic individuals. This goes to support some of what Nassir Ghaemi reported on, that individuals with depression have a better grip on reality. The question then becomes, what reality do they have a better grip on? It seems that in terms of memory recall and attributing mental states, they fare worse than normal controls; but in other tests concerning how much control one has over reality, people with depression fare better than normal people. So it seems that depression cuts both ways in terms of how one relates to reality.

This also personally makes a lot of sense to me considering how bad I am at determining what other people are thinking. I’m terrible at it. I feel there are always too many options and I never know which one to choose. I kind of understand people, but they’re always rather alien to me whenever I’m in a manic state.

What about you? Do you often find it difficult to figure out what people are thinking or feeling when manic or depressed?

 

References:

http://journals.cambridge.org.ezproxy.library.wisc.edu/action/displayAbstract?fromPage=online&aid=5061076

http://www.sciencedirect.com/science/article/pii/S0165032702000083#ref_BIB13

Why Lithium?

Why is lithium the gold standard for treatment in bipolar disorder? What makes it a particularly useful drug? And what does it do in terms of being effective in managing affective disorders?

To start it all off, Lithium is an old drug. It was first used for stones in the bladder way back in 1843, but it wasn’t until 1949 that John Cade discovered that it had anti-manic properties. Lithium’s mechanism has to do with the sodium-potassium levels in neurons. The sodium pump is responsible for potentiating the neuron to receive and amplify incoming messages. Lithium interferes with this process and thus reduces the potentiation of neurons, in effect, it stops certain messages from being relayed. I surmise that this results in the quieting of the manic mind which is firing on all cylinders. But it also works fairly well as an antidepressant. So much so that a randomized trial found no statistically significant difference between lithium and antidepressants in unipolar affective disorder. Lithium, it seems, works both sides of bipolar disorder with gold standard efficacy. It also is highly effective in reducing suicidal tendencies. The difference being a very significant 80%

But what about other effects that lithium has on the brain? I recently wrote a bit about it, but I’ll tread the waters again. Lithium has a restorative property to developmental differences in the hippocampus region of the brain. That region being responsible for emotional regulation and long term memory. So lithium has an advantage in both being a prophylactic treatment that treats the symptoms as well as a restorative role in increasing the brain volume of certain regions of the brain.

So why not lithium. It requires management. For starters, there is a narrow window of therapeutic lithium levels and toxic lithium levels. Therapeutic levels of lithium found in plasma are to be between 0.4 and 1.2 mmol L+ (millimolar of lithium ions), but toxic levels are at 1.5 mmol L+. This means that going on lithium is an investment in time and access to monitoring facilities. You can’t just take it and check the side effects of it, you need to go and have blood tests regularly until you’re in the therapeutic range. If someone is highly unstable, lithium is hardly a drug of choice given that the tests might not be followed through or the titration period will be ignored.

In addition to access to testing facilities, the narrow band of therapeutic versus toxic levels means that one must be careful of things like sweating too much, becoming dehydrated, drinking too much caffeine. Sweating and dehydration increases the lithium levels in the body, where as caffeine reduces them. Life style changes are required for this drug to work. It’s not set-and-forget like lamictal, it’s a drug that requires proactive monitoring of electrolytes, hydration, exercise, weight gain, and food intake.

But despite all of that, it works. And it works very well. I’m only into my first week on it, and I’m being very careful and being the good patient, but I wonder how long that can last. But in the mean time, I have noticed a decrease in my suicidal ideation, so it might be starting to work. Here’s hoping Lithium is the drug of choice. It’s the 11th drug that I’ve been put on in the past 11 months if you count all the benzos, so here’s hoping that it’s the last drug that they put me on.

References:

http://blogs.psychcentral.com/bipolar/2011/02/lithium-increased-brain-volume-bipolar-disorder/

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003492.pub2/abstract

http://www.annualreviews.org/doi/abs/10.1146/annurev.pharmtox.011008.145557

Nicotine May Help Bipolar Disorder and Schizophrenia

In individuals with bipolar disorder and schizophrenia, smoking is heavily present. The British Journal of Medicine found that approximately 56% of those with bipolar disorder smoke; with psychosis, this number jumps to 70%. The Royal College of Psychiatrists found that almost 90% of those with schizophrenia smoke. This is far higher than the national average which the CDC estimates at around 20-25%. So something must be driving the use of tobacco, and in particular nicotine, in these two disorders.

So what’s going on? Is it being driven by the disease or is it self medication. Well, it appears that there is some evidence for self medication. The associated content referencing Science Magazine reports that one of the roles that nicotine is playing is in the GABA receptors. Nicotine bound in the prefrontal cortex and the hippocampus inhibited the enzyme DNMT1, which breaks down GABA, allowing for more GABA to be produced. The effects of nicotine on GABA is profound. In a study conducted by the American College of Neuropsychopharmacology, they found that GABA rose by 10% in the brain after smoking an inhaler and then, 45 minutes later, continued producing GABA at a four-fold rate compared to a normal brain.

So what is this magical GABA and what does it do to the brain. The Associated Content provides a nice outline of what GABA does in the brain:

“GABA is the communications speed controller, making sure all brain communications are operating at the right speed and with the correct intensity”, writes Joseph M. Carver, Clinical Psychologist. When there is too little GABA, we become overstimulated and engage in excessive and impulsive behavior. When there is too much GABA, we become overly relaxed and sedated. The levels of GABA are low in schizophrenia and bipolar disorder as well as in epilepsy and other seizure disorders.”

So that’s what GABA does in our brains, it acts as an inhibitor in the hippocampus region of our brains and slows down the firing of the neurons.

What does this mean for those with schizophrenia and bipolar disorder. For schizophrenia, the results are good. Ripoll et al. found that a 14mg nicotine patch improved sustained focus in schizophrenic patients while there was no gain in control subjects. It was also found to enhance smooth eye movement. Smooth eye movement is a complex task involving the visual cortex and the motor cortex. The complexity of this task is difficult for those with schizophrenia, indicating that cognitive improvements can be measured by how well movement tracking is performed. In more general terms of cognitive enhancement they found that “attention, sensory gating and eye movements, and more generally in cognitive, sensory and memory disorders” were improved with nicotine. In addition to these findings, there are previous studies showing that schizophrenic symptoms return when nicotine intake is reduced.

So the comorbidity of schizophrenia and smoking appear to be self medicative in a positive way. In addition to that Dépatie et al. found that such improvements with a 14mg nicotine patch were not found in the control groups. This indicates that nicotine use in schizophrenia is not merely a matter of habit or addiction, it is a matter of self medication for symptoms.

Now for bipolar disorder. For similar reasons as above mentioned, the impact of increasing GABA in the brain acts as a mood regulator by sedation. Acting as a neurotransmitter inhibitor, the effects of the nicotine slows down the brain and reduces symptoms like anxiety. But this comes with a double edged sword. According to the Journal of Affective Disorders, non-smokers fared better in the Young Mania Rating Scale than smokers did. Indicating that smoking has some negative impacts on mania. Why is this? Serotonin. Nicotine also stimulates the production of other neurotransmitters, such as dopamine, noradrenaline, GABA and glutamate. Serotonin acts as a type of antidepressant for the brain, the same way that SSRIs do operate. So the influx of more serotonin may actually counter act the inhibition due to GABA. However, when depressed, this may be reversed. So depending on what mood you are currently in, nicotine might be beneficial or detrimental to one’s mental health.

But the short term effects of GABA are what primarily interests me in these studies. The sedating and calming effect of nicotine may well be what is needed for short term relief from manic symptoms. And though it may play a role in prolonging mania with elevated serotonin levels, the short term is positively impacted with sedation. Hence the reason for sometimes needing a cigarette to calm down when agitated is so needed while manic.

More work needs to be done on studying the interplay between mental illness and nicotine. There is very little done in studying the effects of nicotine and bipolar disorder, but there is some literature on it regarding schizophrenia. So from what I can glean, the use of tobacco for the nicotine is not something that is merely an addiction that is difficult to shed by a particular class of mental illness, but instead appears to have therapeutic effects as well.

Hope you enjoyed this bit of research.

 

http://www.news-medical.net/news/2007/12/10/33328.aspx

http://www.cdc.gov/chronicdisease/resources/publications/AAG/osh.htm

http://www.ncbi.nlm.nih.gov/pubmed/11435266

http://apt.rcpsych.org/content/6/5/327.full

http://www.medscape.com/viewarticle/483888_4

http://www.associatedcontent.com/article/1690861/why_nicotine_calms_the_brain_in_schizophrenia_pg2.html?cat=70

http://www.medwire-news.md/47/76704/Psychiatry/Smoking_interferes_with_treatment_for_bipolar_mania.html

http://www.jad-journal.com/article/S0165-0327(08)00038-4/abstract